Four new indole-diterpene alkaloids asperindoles A–D (1–4) and the known p-terphenyl derivative 3″-hydroxyterphenyllin (5) were isolated from the marine-derived strain of the fungus Aspergillus sp., associated with an unidentified colonial ascidian. The structures of 1–5 were established by 2D NMR and HRESIMS data. The absolute configurations of all stereocenters of 1–4 were determined by the combination of ROESY data, coupling constants analysis, and biogenetic considerations. Asperindoles C and D contain a 2-hydroxyisobutyric acid (2-HIBA) residue, rarely found in natural compounds. Asperindole A exhibits cytotoxic activity against hormone therapy-resistant PC-3 and 22Rv1, as well as hormone therapy-sensitive human prostate cancer cells, and induces apoptosis in these cells at low-micromolar concentrations.

Three new epidithiodiketopiperazines pretrichodermamides D–F (1–3), together with the known N-methylpretrichodermamide B (4) and pretrichodermamide С (5), were isolated from the lipophilic extract of the marine algae-derived fungus Penicillium sp. KMM 4672. The structures of compounds 1–5 were determined based on spectroscopic methods. The absolute configuration of pretrichodermamide D (1) was established by a combination of modified Mosher′s method, NOESY data, and biogenetic considerations. N-Methylpretrichodermamide B (5) showed strong cytotoxicity against 22Rv1 human prostate cancer cells resistant to androgen receptor targeted therapies.

A new melatonin analogue 6-hydroxy-N-acetyl-β-oxotryptamine (1) was isolated from the marine-derived fungus Penicillium sp. KMM 4672. It is the second case of melatonin-related compounds isolation from microfilamentous fungi. The neuroprotective activities of this metabolite, as well as 3-methylorsellinic acid (2) and 8-methoxy-3,5-dimethylisochroman-6-ol (3) from Penicillium sp. KMM 4672, candidusin A (4) and 4″-dehydroxycandidusin A (5) from Aspergillus sp. KMM 4676, and diketopiperazine mactanamide (6) from Aspergillus flocculosus, were investigated in the 6-hydroxydopamine (6-OHDA)- and paraquat (PQ)-induced Parkinson’s disease (PD) cell models. All of them protected Neuro2a cells against the damaging influence of 6-OHDA to varying degrees. This effect may be realized via a reactive oxygen species (ROS) scavenging pathway. The new melatonin analogue more effectively protected Neuro2A cells against the 6-OHDA-induced neuronal death, in comparison with melatonin, as well as against the PQ-induced neurotoxicity. Dehydroxylation at C-3″ and C-4″ significantly increased free radical scavenging and neuroprotective activity of candidusin-related p-terphenyl polyketides in both the 6-OHDA- and PQ-induced PD models.

Low molecular weight secondary metabolites of marine fungi Aspergillus flocculosus, Aspergillus terreus and Penicillium sp. from Van Phong and Nha Trang Bays (Vietnam) were studied and a number of polyketides, bis-indole quinones and terpenoids were isolated. The structures of the isolated compounds were determined by 1D and 2D NMR and HR-ESI-MS techniques. Stereochemistry of some compounds was established based on ECD data. A chemical structure of asterriquinone F (6) was thoroughly described for the first time. Anthraquinone (13) was firstly obtained from a natural source. Neuroprotective influences of the isolated compounds against 6-OHDA, paraquat and rotenone toxicity were investigated. 4-Hydroxyscytalone (1), 4-hydroxy-6-dehydroxyscytalone (2) and demethylcitreoviranol (3) have shown significant increasing of paraquat- and rotenone-treated Neuro-2a cell viability and anti-ROS activity.

Marine sediments are characterized by intense degradation of sedimenting organic matter in the water column and near surface sediments, combined with characteristically low temperatures and elevated pressures. Fungi are less represented in the microbial communities of sediments than bacteria and archaea and their relationships are competitive. This results in wide variety of secondary metabolites produced by marine sediment-derived fungi both for environmental adaptation and for interspecies interactions. Earlier marine fungal metabolites were investigated mainly for their antibacterial and antifungal activities, but now also as anticancer and cytoprotective drug candidates. This review aims to describe low-molecular-weight secondary metabolites of marine sediment-derived fungi in the context of their biological activity and covers research articles published between January 2016 and November 2020.

Four new compounds were isolated from the Vietnamese marine sediment-derived fungus Aspergillus flocculosus, one aspyrone-related polyketide aspilactonol G (2), one meroterpenoid 12-epi-aspertetranone D (4), two drimane derivatives (7,9), together with five known metabolites (1,3,5,6,8,10). The structures of compounds 1–10 were established by NMR and MS techniques. The absolute stereoconfigurations of compounds 1 and 2 were determined by a modified Mosher’s method. The absolute configurations of compounds 4 and 7 were established by a combination of analysis of ROESY data and coupling constants as well as biogenetic considerations. Compounds 7 and 8 exhibited cytotoxic activity toward human prostate cancer 22Rv1, human breast cancer MCF-7, and murine neuroblastoma Neuro-2a cells.